Optical Phased Array-Based Optical Tweezers Manipulate Cells without Damaging Them

Compared to bulk optical tweezers, integrated optical tweezers are compact and low-cost, making them practical for most research organizations. But so far, integrated optical tweezers have been of limited use in biological research, due to the very small standoff distances they provide.

To increase the standoff distance, researchers at MIT used an integrated optical phased array (OPA). The silicon photonics-based OPA enables trapping and tweezing of biological particles at 5 mm above the chip surface, enlarging the standoff distance by more than two orders of magnitude. The OPA tweezers can capture and manipulate biological particles from a safe distance while the particles remain inside a sterile cover slip. Both the chip and the particles are protected from contamination.

The OPA optical tweezers offer the advantages of integrated tweezers along with much of the functionality of bulk optical systems. Someday, the OPA tweezers could be used to study DNA, classify cells, investigate disease mechanisms, and perform experiments not possible with prior implementations of integrated tweezers.

“This work opens up new possibilities for chip-based optical tweezers by enabling trapping and tweezing of cells at much larger distances than previously demonstrated,” professor Jelena Notaros said.

Chip-based optical tweezers that use an intensely focused beam of light to capture and manipulate biological particles without damaging the cells could help biologists study the mechanisms of diseases. Courtesy of MIT/Sampson Wilcox.

The OPA is used to focus the light emitted by the chip at a specific point in the radiative near field of the chip. It provides a steerable potential energy well in the plane of the sample that can be used to trap and tweeze microscale particles.

The OPA consists of a series of microscale antennas fabricated on a chip using semiconductor manufacturing processes. By electronically controlling the optical signal emitted by each antenna, the researchers can direct the OPA to shape and steer the beam emitted by the chip.

Most integrated OPAs developed to date are not designed to generate the tightly focused beams needed for optical tweezing. The MIT team found that, by creating specific phase patterns for each antenna, it could form an intensely focused beam suitable for optical trapping and tweezing several mm from the chip’s surface. By varying the wavelength of the optical signal that powers the chip, the researchers can steer the focused beam over a range larger than 1 mm with microscale accuracy.

“No one had created silicon photonics-based optical tweezers capable of trapping microparticles over a millimeter-scale distance before,” Notaros said. “This is an improvement of several orders of magnitude higher compared to prior demonstrations.”

The researchers used the OPA optical tweezers to trap polystyrene microspheres 5 mm above the surface of the chip and calibrate the optical trap system. They nonmechanically steered the focal spot of the beam by varying the input laser wavelength. They changed the system from a static optical trap to dynamic optical tweezers and demonstrated tweezing of polystyrene microspheres in one-dimensional patterns with high fidelity and submicron precision.

The team also used the tweezers to show controlled deformation of mouse lymphoblast cells, performing, to the best of its knowledge, the first cell experiments using single-beam integrated optical tweezers.

Traditionally, optical tweezers have required a large microscope setup in a lab and multiple devices to form and control light. Chip-based optical tweezers offer a compact, mass-manufacturable, broadly accessible, high-throughput alternative to bulk systems for optical manipulation.

“With silicon photonics, we can take this large, typically lab-scale system and integrate it onto a chip,” Notaros said. “This presents a great solution for biologists, since it provides them with optical trapping and tweezing functionality without the overhead of a complicated bulk optical setup.”

Given the natural scalability and design flexibility of the CMOS-compatible fabrication platform used to produce the OPA tweezers, the researchers envision numerous ways to evolve the system to improve its performance and enable new functionality. The team wants to refine the system to enable an adjustable focal height for the light beam. It also wants to apply the device to different biological systems and use multiple trap sites simultaneously to manipulate biological particles in more complex ways.

By extending focal heights to the millimeter scale, the team has introduced a new modality for integrated optical tweezers, significantly expanding the use and compatibility of tweezers for biological experiments and emerging in vivo trapping research. Promising applications where the OPA optical tweezers could be useful range from DNA and protein experiments to cell manipulation and sorting.

“Having these systems widely available will allow us to study fundamental problems in single-cell biophysics in ways previously only available to a few labs, given the high cost and complexity of the instrumentation,” University of Rochester professor Ben Miller, who was not involved in the research, said. “I can also imagine many applications where one of these devices, or possibly an array of them, could be used to improve the sensitivity of disease diagnostic.”

The research was published in Nature Methods (www.doi.org/10.1038/s41467-024-52273-x).